This application for a Mentored Patient-Oriented Research Career Developmental Award (K23) seeks support for Akihiko Saitoh, M.D., who is currently a Clinical Instructor in Pediatric Infectious Diseases at University of California, San Diego. Under the mentorship of Stephen A. Spector, M.D., Dr. Saitoh will continue to pursue his investigation into the human leukocyte antigen (HLA) that impact on the response to highly active antiretroviral therapy (HAART) in human immunodeficiency virus type-1 (HIV-1) infected children. An additional period of support for clinical research under Dr. Spector's mentorship will allow Dr. Saitoh to expand his repertoire of skills in the field of immunology related to HIV-1. Development of these skills will be essential to help ensure that Dr. Saitoh will succeed in achieving his long-term career goal of becoming an independent physician scientist in an academic medical institution. In this application, Dr. Saitoh proposes to investigate the relationship between HLA class I and class II polymorphisms and the response to HAART in HIV-1 infected children. The specific aims of this proposal are: Aim I: To determine the influence of HLA class I alleles in response to HAART in HIV-1 infected children. Aim II: To evaluate escape mutants through cytotoxic T lymphocyte (CTL) in the specific HLA restricted sites in HIV-1 infected children with virologic failure. Aim III: To determine the influence of HLA class II alleles in response to HAART in HIV-1 infected children. The information learned from this research will help to predict rates of the response to HAART depending upon a child's HLA polymorphisms and has the potential to enable antiretroviral therapy to be optimized for the treatment of a given child with the least toxicity. This research will also suggest modes of pathogenesis that can lead to the development of vaccine strategies.